Adenosine uptake is the major effector of extracellular ATP toxicity in human cervical cancer cells.
Bottom Line: Corroborating these data, blockage or knockdown of P2 × 7 only slightly reduced ATP cytotoxicity.Moreover, ATP-induced apoptosis and signaling-p53 increase, AMPK activation, and PARP cleavage-as well as autophagy induction were also inhibited by dipyridamole.In addition, inhibition of adenosine conversion into AMP also blocked cell death, indicating that metabolization of intracellular adenosine originating from extracellular ATP is responsible for the main effects of the latter in human cervical cancer cells.
Affiliation: Laboratory of Biochemical and Cytological Analysis, Faculty of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil.Show MeSH
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Mentions: Because lower levels of P2×7 were described in epithelial cancer cells than in normal tissue (Li et al., 2009), we investigated the levels of P2×7 mRNA in different cervical cancer cell lines and in an immortalized human epithelial cell line (HaCaT) used as nontumorigenic control cells (Figure 1A). Cervical cancer cell lines (SiHa, HeLa, and C33A) and HaCaT exhibited different amounts of P2×7 mRNA. Among them, the SiHa cell line presented the highest levels of P2×7 mRNA, and therefore we chose it to investigate the role of P2×7 in the response of cervical cancer to extracellular ATP.
Affiliation: Laboratory of Biochemical and Cytological Analysis, Faculty of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, RS 90610-000, Brazil.